This application is a 371 of PCT/N298/00064 filed May 27, 1998.
The present invention relates to improvements in and/or relating to intra-vaginal devices suitable for insertion and retention within pigs.
Intra-vaginal devices are frequently used to deliver an active substance into an animal.
One use of intra-vaginal devices is to control the breeding cycles of animals. In this respect under the trade mark CIDR(trademark) this company has manufactured a variery of devices for different animals including but not limited to cattle, sheep and pigs. The prior art devices of this company where they are to be used to synchronise oestrus have usually involved a spine (for example of a nylon plastics material) and an at least partially encasing silicone rubber matrix that has been impregnated with the active substance to be released, eg. progesterone.
The prior art device of this company marketed under the trade mark CIDR(trademark) for pigs is detailed in New Zealand Letters Patent No. 230023 of which the Australian and U.S. equivalents are respectively numbers AUS620523 and U.S. Pat. No. 5,217,450. Appended hereto in the annexed drawings (FIGS. 4A to 4C) are representations of such a prior art form from which it will be seen that a complex construction having wall engaging means at each end has been hitherto required in order to obtain a good measure of retention. In addition a complex construction for the non cervix end was required whereby the retention device at that end could be configured in three different ways, only one of which was its retention condition.
With pigs a great deal of care is required in order to ensure retention against spontaneous ejection and also against withdrawal by another animal.
The full content of the aforementioned patent specifications are hereby here included by way of reference.
The literature adequately explains the purposes for which such intra-vaginal devices containing progesterone or progestagens are delivered into female animals prior to mating.
In addition reference should be made, by way of example, to proprietary information released by suppliers of such active substances including, by way of example, VIRBAC in respect of its SUIPROST(trademark) injectable product which is a synthetic prostaglandin for induction and synchronisation of farrowing in sows. The role however of such intra-vaginal devices usually is to be much earlier, namely, in respect of synchronising the onset of oestrus.
If both the control of oestrus cycle and high fertility are desired in the pigs then an intra-vaginal insert must deliver sufficient progesterone. We know that 15, 25, 50 mg per day (IM) for 14 days results in control of the oestrus cycle. However poor fertility results. We believe a dose of 100 mg per day for 14 days (IM) is desirable to both control the oestrus cycle and give normal fertility.
The present invention is therefore directed to porcine intra-vaginal devices that feature an improved retention characteristic (eg; across hymenal ring positioning and vestibular deployment of retention means), is of sufficient surface area as far as progesterone impregnated matrix or matrices is concerned and/or can deliver progesterone (at least) on both sides of the hymenal ring.
The amount of progesterone delivered by the said device preferably should be at least sufficient to maintain a plasma level of in excess of 4 ng/mL (as measured in an ovariectomised animal over at least a 14 day insertion period).
The present invention in one aspect is directed toward an intra-vaginal device which provides an alternative to the aforementioned prior art device. A preferred device is believed to provide a simplicity of moulding in at least some of its forms whilst providing in such preferred forms enhanced retention characteristics irrespective of the variations within the vaginal tracts of different pigs.
The present invention in other aspects relates to the control of the onset of oestrus and/or the maintenance or enhancement of fertility of pigs (particularly gilts).
In a first aspect the invention consists in a porcine intra-vaginal device of a shape and size adapted to be positionable in the vaginal tract across the hymenal ring of a target animal (eg; a gilt) to extend to both sides of the hymenal ring of the animal, the device having or being (at least in part) a progesterone impregnated matrix or matrices to be on at least either side of the hymenal ring and being at least 150 cm2 in total area.
Preferably said total area of progesterone impregnated matrix or matrices is greater than 172 cm2.
Preferably said matrix or matrices carry a progesterone load of at least 1.9 g.
Preferably said progesterone load is from 1.9 to 2.5 g.
Preferably, for gilts, said progesterone load is about 2.2 g.
Preferably said progesterone load is at least substantially all carried by the matrix or matrices within 1.2 mm of its release surface.
Preferably the device has a nylon (or equivalent) spine with an impregnated matrix formed thereabout.
Preferably the device has variable geometry means which deploy or is deployable upon insertion to retain the device in the vaginal tract. The variable geometry means may deploy on either or both sides of the hymenal ring.
Preferably the variable geometry means comprise at least one resilient wing or a form collapsible under the action of withdrawal.
Preferably the device is elongate of body with a wasted region to lie on the hymenal ring.
Preferably the matrix is a progesterone containing silicone rubber material which has been formed by injection of the uncured progesterone containing matrix as a liquid into a mould for a sufficient time to achieve a mould temperature or temperatures within the range of from 100xc2x0 C. to 210xc2x0 C. and a shape retaining at least partial cure thereof.
In a second aspect the invention consists in a porcine intra-vaginal device of a shape and size adapted to be positionable in the vaginal tract across the hymenal ring of a target animal (eg; a gilt) to extend to both sides of the hymenal ring of the animal, the device having or being (at least in part) a progesterone impregnated matrix or matrices to be on at least either side of the hymenal ring, the device having variable geometry means which deploy in the vestibule upon insertion to retain the device in the vaginal tract.
Preferably said matrix or matrices are at least 150 cm2 in total area.
Preferably said total area of progesterone impregnated matrix or matrices is greater than 172 cm2.
Preferably said matrix or matrices carry a progesterone load of at least 1.9 g.
Preferably said progesterone load is from 1.9 to 2.5 g.
Preferably, for gilts, said progesterone load is about 2.2 g.
Preferably said progesterone load is at least substantially all carried by the matrix or matrices within 1.2 mm of its release surface.
Preferably the device has a nylon (or equivalent) spine with an impregnated matrix formed thereabout.
Preferably the matrix is a progesterone containing silicone rubber material which has been formed by injection of the uncured progesterone containing matrix as a liquid into a mould for a sufficient time to achieve a mould temperature or temperatures within the range of from 100xc2x0 C. to 210xc2x0 C. and a shape retaining at least partial cure thereof.
In another aspect the present invention consists in an intra-vaginal device having an elongate body (preferably not articulated) to be inserted in a pig with part on either side of the hymenal ring of a pig and having variable geometry retention means dependent from that part of the elongate body to be located in the vestibule of the vaginal tract, said variable geometry retention means being capable of assuming a vestibule engagement form after release from an insertion mode.
Preferably said vestibule geometry retention means is or are capable of assuming a third mode, ie. a withdrawal mode upon the application of an external force to part of said device within said vestibule or to any means dependent therefrom extending towards and/or through the vulva.
Preferably said variable geometry retention means are in the form of wing members.
Preferably said resilient members are in the forms of wings which assume in their vestibular engagement mode a condition such that spasm of the vestibular wall of an animal into which the device has been inserted is unlikely to provide a sufficient component of force on the inserted device to cause ejection from the vaginal tract.
Preferably said variable geometry retention means in said vestibular engagement mode engages into folds at least momentarily present in the vestibule wall of the animal into which it has been inserted.
Preferably the variable geometry retention means is such that spasm of the vaginal tracts and in particular the vestibule of the animal into which the device has been inserted is such as to provide no significant net force away from the cervix on the device.
Preferably with a view to meeting the aforementioned functional requirements concerning retention, most preferably the variable geometry retention means is in the form of wings (preferably two, which are preferably opposed), each of which, in its deployed vestibular engagement mode, has a distal end closer to the vulva than that region of that part of the elongate body of the device from which that particular wing projects.
Preferably the device includes a reduced section or an effective reduced section (if for example the device is fluted or otherwise) over that region of the elongate body of the device adjacent the variable geometry retention means dependent therefrom but which is adapted to lie within the hymenal ring of the animal when the device is in its retained condition.
Preferably the device or at least parts thereof (for example at least the vaginally received part of the elongate body carries or is a matrix impregnated with or carrying a substance to be released to the animal.
Preferably the construction of the device is such that it does not extend into the cervix during normal insertion operations and such that upon normal insertion where it is retained by said variable geometry retention means such variable geometry retention means and/or the configuration of the elongate body of the device is such as to prevent sufficient movement through the hymenal ring to allow the end of the device to enter the cervix.
Preferably that part of the elongate body which carries the variable geometry retention means includes means capable of being engaged by a device withdrawal tool (or by other means).
Preferably the device is one that includes at least one or more of the following parameters
(i) at least a surface area greater than 180 cm2 of a progesterone impregnated matrix,
(ii) a length of from 9.0 cm to 15.0 cm (and preferably about 11.0 cm) for that region to extend during normal use in a pig from the hymenal ring towards the cervix and/or to extend for a distance of from 4.5 cm to 8.0 cm (preferably about 5.5 cm) during normal use from the hymenal ring to the vulva opening,
(iii) a maximum cross-sectional area (other than in respect of the variable geometry retention means) of from 2.5 cm2 to 4.5 cm2,
(iv) a reduction in cross-sectional area for that region of the elongate body adapted to be positioned at the hymenal ring so as to have a maximum cross sectional dimension of from 1.5 cm to 3.5 cm (preferably about 2.5 cm),
(v) at least one flute or the like providing form provided in that zone to be positioned in the vestibule,
(vi) at least one opening in at least one of the flute forming shapes to allow the insertion of a withdrawal tool,
(vii) at least one flute or the like providing form extending longitudinally of that region of the elongate body to be located within the vagina proper.
Preferably the loading of the impregnated matrix is with from 1.9 to 2.5 grams of progesterone (preferably about 2.0 grams progesterone).
Irrespective of the loading or surface area of the device and/or the depth of any impregnated matrix (whether an encasing matrix on a structural spine or not, or a shape holding impregnated matrix itself without a separate spine) it is capable over a period of from 7 to 14 days in an average gilt being prepared for the onset of oestrus upon withdrawal of the device of maintaining a blood plasma level equating to a blood plasma level in excess of 4 ng/mL measured in an ovarectomised animal.
In a different aspect the invention consists in an intra-vaginal device for delivering a substance into a pig (preferably at least substantially via the vaginal mucous and membrane),
said device comprising
an elongate body (preferably non articulating) having a withdrawal end and an insertion and capable of traversing the hymenal ring of the pig with the withdrawal end in the vestibule and the insertion end in the vaginal cavity, and
at least one wing like structure capable of self deployment (e.g. resiliently) from an insertion condition into a membrane engaging condition to resist spontaneous ejection of the device, the membrane being selected from one or more of
(i) vestibular membrane,
(ii) hymenal ring membrane, and
(iii) vaginal membrane.
Preferably said device is one as previously defined in any of its forms.
In yet a further aspect the present invention consists in a pack which includes a plurality of intra-vaginal devices in accordance with the present invention and preferably also at least one applicator and/or withdrawal tool therefor.
Preferably said pack includes directions of use.
In yet a further aspect the present invention consists in a method of delivering a substance into a female pig which comprises
inserting a device as previously defined into the vaginal tract of the pig so as to release a substance from the device whilst resident therein, the device resisting spontaneous ejection by means of the deployment of said variable geometry retention means (preferably within the vestibule so as to engage the wall or walls thereof).
Preferably said device is as defined in any of its forms previously described and is inserted in a female pig (eg gilt) for a period of from 7 to 18 days where it maintains substantially over its insertion period a blood plasma level of progesterone equating to a progesterone blood plasma level in excess of 4 ng/mL measured in an ovariectomised animal, and whereupon, upon its withdrawal, will ensure within 3 to 5 days thereafter the onset of oestrus in the female pig.
Preferably the withdrawal is achieved by hooking a tool wire or other apparatus into the vestibular end region of the device and withdrawing the same.
Preferably said device is not capable of normally being reached by another pig once correctly inserted in a pig.
Preferably said device is inserted while at least having the variable retention means temporarily constrained to lie against part of the elongate body.
Preferably said variable geometry retention means are wings that during normal insertion and normal retention are angled from the elongate body with their distal ends nearer the vulva than those ends connected to the elongate body but (preferably) which pass over a condition substantially normal to the elongate axis of the elongate body of the device at the time of or during withdrawal so as to angle more towards the hymenal ring than to the vulva.
Preferably the method involves positioning the device such that a reduced section along the length of the elongate body of the device is in the zone of the hymenal ring and the variable geometry retention means is in the vestibule but may on occasions nevertheless result in retention being achieved with the variable geometry retention device accidentally having been inserted on the vaginal side of the hymenal ring (or at least the device has that capability) at least until moved under action of the pig to properly deploy the variable geometry retention means within the vestibule.
In a further aspect the present invention consists in, in a number of female pigs, the act of at least inserting and retaining for a period of time (and optionally removing the same prior to slaughter, eg. as might be required for mating or farrowing) a device as previously defined and wherein at least a majority of the devices are inserted such that said variable geometry retention means deploys and engages the wall of the vestibule between the vulva entrance and the hymenal ring rather than the hymenal ring itself or the vaginal wall on the vaginal side of the hymenal ring.
In still a further aspect the present invention consists in a plurality of female pigs each which has had a device as previously defined inserted into the vaginal cavity thereof by a method in accordance with the present invention.
Preferably said pigs have a progesterone blood serum level whilst the device is resident in their vaginal tract equating to a blood plasma level in excess of 4 ng/mL measured in an ovarectomised animal.
To those skilled in the art to which the invention relates, many changes in construction and widely differing embodiments and applications of the invention will suggest themselves without departing from the scope of the invention as defined in the appended claims. The disclosures and the descriptions herein are purely illustrative and are not intended to be in any sense limiting.